Divergent Fates of Hardjo Leptospires: Early Transcriptomic Response of Leptospira interrogans in an Ovine Dialysis Membrane Chamber Model.

Leptospira interrogans serovar Hardjo and Leptospira borgpetersenii serovar Hardjo are major bovine- and ovine-adapted pathogens that differ markedly in genome content. To investigate early events during host exposure, we compared the survival of both species using an ovine peritoneal dialysis membrane chamber (DMC) model, which exposes leptospires to simultaneous nutrient restriction, temperature and osmotic shifts and small host-derived immune factors such as antimicrobial peptides (AMPs). L. borgpetersenii failed to survive 24 h of in vivo exposure, whereas L. interrogans persisted and remained viable. RNA sequencing of two L. interrogans strains revealed extensive transcriptional reprogramming, with 1066 differentially expressed genes (DEGs). Early host exposure triggered coordinated remodelling of membrane-associated proteins, including strong induction of adhesins (LigA/B and LenC/F) and other lipoproteins, accompanied by metabolic reprogramming that redirects cellular resources towards conservation and membrane reorganisation. Iron-related genes were also differentially regulated, and L. borgpetersenii showed reduced survival under in vitro iron-limiting conditions. A substantial proportion of downregulated genes belonged to pathways governing signal transduction, chemotaxis and motility, indicating early suppression of selected sensory and locomotive functions. Many of the genes most strongly regulated under experimental stress conditions lack orthologues in the L. borgpetersenii genome, suggesting that genome reduction has eliminated factors required for survival of the stressors encountered in this model, which further implies that this species relies on distinct early-phase survival strategies that do not support extracellular persistence under the conditions tested. Our findings show that L. interrogans serovar Hardjo rapidly modulates cellular networks to promote early survival in body fluids or within the extracellular matrix.